DNA-based nanotechnology stimulates potent antitumor immune responses

Researchers designed DLnano-vaccines displaying 60 copies of protein parts derived from the melanoma-specific antigens Trp2 and Gp100 and tested these in mouse models of melanoma, observing prolonged survival that depended on CD8 T cell activation both in therapeutic and prophylactic settings.

“One of the advantages of synthetic DNA technologies over other methods is the versatility of the platforms,” said Ziyang Xu, Ph.D., a recent doctoral graduate working at Wistar and the first author of the study. “DLnano-vaccines may be designed for various cancer targets and our study shows this is a promising strategy for cancer immunotherapy that may warrant further testing.”

To elucidate the mechanism through which DLnano-vaccines activate CD8 T cells, the team studied the effects of the DNA-launched version of a previously described HIV nanoparticle vaccine (eOD-GT8-60mer). They observed that DLnano-vaccines administered via electroporation resulted in transient muscle cell apoptosis that attracted macrophage infiltration at the injection site, which in turn was instrumental to activate CD8 T cells.

DLnano-vaccines were developed using synthetic DNA technology in collaboration with the lab of David B. Weiner, Ph.D., Wistar executive vice president, director of the Vaccine & Immunotherapy Center, and the W.W. Smith Charitable Trust Professor in Cancer Research and also a co-senior author on the study.

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Co-authors: Neethu Chokkalingam, Edgar Tello-Ruiz, Mamadou A. Bah, Susanne Walker, and Nicholas J. Tursi from Wistar; Megan C. Wise, Paul D. Fisher, Katherine Schultheis, Kate E. Broderick, and Laurent Humeau from Inovio Pharmaceuticals, Inc.

Work supported by: National Institutes of Health (NIH) grants U19 Al109646 and Collaborative Influenza Vaccine Innovation Centers (CIVICs) contract 75N93019C00051; additional support was provided by Inovio Pharmaceuticals, Inc., a grant from the W.W. Smith Charitable Trust, and the Monica H.M. Shander Memorial Fellowship.

Publication information: A DNA-launched nanoparticle vaccine elicits CD8+ T-cell immunity to promote in vivo tumor control, Cancer Immunology Research, 2020. Online publication.

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